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Articles in PresS, published online ahead of print April 23, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00046.2002
Submitted on February 1, 2002
Accepted on April 15, 2002
1 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, Bethesda, MD, USA
2 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, Bethesda, MD, USA; Laboratory of Cellular and Molecular Physiology, Universidad de los Andes, Santiago, Chile
3 Department of Cell Biology, Georgetown University Medical Center, Washington, DC, USA
* To whom correspondence should be addressed. E-mail: caiq{at}nhlbi.nih.gov.
Renal inner medullary cells survive and function despite interstitial osmolality that ranges from 600 to 1700 mosmol/kg, or more. In contrast, much smaller changes kill cells in tissue culture. We defined factors that might account for the difference, using second passage mouse inner medullary epithelial cells. Most of the factors that we tested have no significant effect, including addition of hormones (IGF-I, EGF or ddAVP), growth on porous supports, and presence of matrix proteins (collagen I, collagen IV, fibronectin, laminin or fibrillar collagen I). However, the time course of the change makes a major difference. When osmolality increases from 640 to 1640 mosmol/kg by adding NaCl and urea in a single step, only 30% of cells survive for 24 hours. However, when the same increase is made linearly over 20 hours, 89% of the cells remain viable 24 hours later. We conclude that gradual changes in osmolality, like in vivo, allow cells to survive much greater changes than do the step changes routinely used in cell culture experiments.
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